Volume 13 Supplement 1
Impaired L-type Ca2+ channel function in the dystrophic heart
© Koenig et al; licensee BioMed Central Ltd. 2012
Published: 17 September 2012
Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is an inherited disease characterized by progressive muscle weakness and degeneration. Besides the relatively well described skeletal muscle degenerative processes, DMD is associated with cardiovascular complications including cardiomyopathy and cardiac arrhythmias. The current understanding of the patho-mechanisms is still very limited, but recent research suggests, that dysfunctional ion channels in dystrophic cardiomyocytes considerably contribute to the cardiovascular complications.
By using the whole cell patch clamp technique, the functional properties of voltage-gated L-type Ca2+ channels were studied in ventricular cardiomyocytes derived from normal and dystrophic mice. Physiological consequences were followed up by investigating action potentials and by comparing surface ECG recordings in wild-type and dystrophic mice. Besides the commonly used dystrophin-deficient mdx mouse model, this study is amongst the first to additionally include the dystrophin-utrophin double-deficient mouse model for DMD.
We found that the voltage-dependent inactivation of L-type Ca2+ channels is significantly reduced in dystrophic cardiomyocytes. Moreover, in cardiomyocytes derived from dystrophic adult animals, current density levels are significantly increased. Action potential duration was not prolonged in dystrophic murine cardiomyocytes, but incorporating the observed reduction in current density into a computer model of a human cardiomyocyte resulted in a marked prolongation. Physiological relevance was further suggested by an acceleration of atrioventricular nodal conduction and a prolongation of ventricular repolarisation in the ECG.
L-type Ca2+ channels are significantly impaired in dystrophic cardiomyocytes and likely contribute to the cardiovascular complications associated with Duchenne muscular dystrophy.
This work was supported by the Austrian Science Fund (FWF, grant P23060).
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.